The present invention relates to N-(heterocyclyl)benzene- or -pyridinesulphonamide derivatives, to their preparation and to their therapeutic application.
The compounds of the present invention correspond to formula [I]: 
in which:
X represents either a group xe2x95x90CR4xe2x80x94 or a nitrogen atom,
W represents a xe2x80x94(CH2)2xe2x80x94, xe2x80x94(CH2)3xe2x80x94, xe2x80x94CH2xe2x80x94Cxe2x89xa1Cxe2x80x94 (triple bond) or xe2x80x94CH2xe2x80x94CHxe2x95x90CHxe2x80x94 (double bond in cis or trans configuration) group,
R2 represents
either a piperidyl group which is optionally substituted:
with one or two groups chosen from hydroxyl, (C1-C4)alkyl, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy(C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkylthio, monofluoromethyl, difluoromethyl, trifluoromethyl and (C3-C6)cycloalkyl group,
with a group xe2x95x90CYZ [Y and Z being chosen, independently of each other, from hydrogen atoms, halogen atoms and (C1-C4)alkyl groups (optionally substituted with 1 to 3 halogen atoms)],
with a group: 
xe2x80x83(r=1 to 3) or
with a spiro[(C3-C6)cycloalkane] group,
or a 1,2,3,6-tetrahydropyridyl group optionally substituted with a (C1-C4)alkyl group (this (C1-C4)alkyl group being optionally substituted with 1 to 3 halogen atoms) or a (C3-C6)cycloalkyl group,
or a hexahydro-1H-azepinyl group optionally substituted in position 4 with a trifluoromethyl or difluoromethylene group,
or a heptahydroazocin-1-yl group,
or an octahydro-1H-azonin-1-yl group,
or a group 
xe2x80x83(a-b being a group xe2x80x94CONRxe2x80x2xe2x80x94, m=1 to 2, p=1 to 2 and
Rxe2x80x2 is a hydrogen atom or a (C1-C4)alkyl group),
or a group 
xe2x80x83in which
either R12 is a (C1-C4)alkyl group, a carboxy(C1-C4)alkyl group or a (C1-C4)alkoxycarbonyl(C1-C4)alkyl group and R13 is a (C1-C4)alkoxy or (C1-C4)alkyl group, or R12 is a (C1-C4)alkyl or xe2x80x94CH2CF3 group and R13 is a
group 
xe2x80x83(Q being a carbon or nitrogen atom and r=1 to 3),
or a piperazinyl group optionally substituted with a (C1-C4)alkyl group or a (C1-C4)alkylsulphonyl group,
or a morpholinyl group,
R4 represents
either a halogen atom,
or a hydrogen atom,
R3 represents
either a (C1-C5)alkyl group,
or a group xe2x80x94COR1, in which R1 is either a hydrogen atom or a group (C1-C4)alkyl, xe2x80x94(CH2)nOCH3, xe2x80x94CH2O(C2H4O)nCH3, xe2x80x94(CH2)nCF3 or xe2x80x94(CH2)nOH (n=1 to 4),
or a group xe2x80x94SO2R5,
or a group xe2x80x94CONHR5,
or a group xe2x80x94SO2N(R5)2, in which R5 is a (C1-C4)alkyl group,
A represents
either a phenyl group optionally substituted with 1 to 3 substituents chosen from
a halogen atom and
groups (C1-C4)alkyl, (C1-C4)alkoxy, trifluoromethyl, trifluoromethoxy, xe2x80x94CH2OR10, xe2x80x94CH2OCOR10, xe2x80x94CH2OCONR10R11, xe2x80x94COOR10, xe2x80x94CONR10R11, nitro, xe2x80x94NR10R11, xe2x80x94NHCOR10 and xe2x80x94NH(CH2)qOR10, in which R10 and R11 are, independently of each other, a hydrogen atom or a (C1-C4)alkyl group and q is between 0 and 6,
or a heterocycle chosen from pyridyl, thienyl, furyl, pyrimidinyl and thiazolyl groups, the said groups possibly being substituted like the phenyl group above,
or a (C5-C8)cycloalkyl group, and B represents
either a pyridyl group optionally substituted with 1 or 2 substituents chosen from a (C1-C4)alkyl group, a hydroxyl group and a (C1-C4)alkoxy group,
or an aminopyrazinyl group,
or an aminopyridazinyl group,
or a pyrimidinyl group optionally substituted with an amino group,
or a piperidyl group,
or an aminopyridyl group optionally substituted on the pyridine with a (C1-C4)alkyl or (C1-C4)alkoxy group or a halogen atom, the amino group possibly also being substituted with a (C1-C4)alkyl group,
or an aminophenyl group, the amino group possibly being substituted with a (C1-C4)alkyl group and the phenyl group possibly being substituted with a (C1-C4)alkyl group or a halogen atom.
In the context of the invention, the terms below have the following meanings:
a (C1-C4)alkyl group is a linear or branched, saturated hydrocarbon-based chain containing from 1 to 4 carbon atoms,
a (Cx-Cy)cycloalkyl group is a cyclic hydrocarbon-based chain containing from x to y carbon atoms,
a (C1-C4)alkoxy group is an oxygen radical substituted with a (C1-C4)alkyl group defined above,
a halogen atom is a chlorine, bromine, iodine or fluorine atom.
In the context of the invention, the halogen atoms are preferably chlorine, fluorine and bromine.
Depending on the nature of the group W, the compounds of formula (I) in accordance with the invention may be represented by formulae (I1), (I2), (I3) and (I4) below: 
The compounds that are preferred according to the invention are the compounds of formula [I] in which:
X, W, R4, A and B are as defined above,
R2 represents
either a piperidyl group which is optionally substituted:
with one or two groups chosen from hydroxyl, (C1-C4)alkyl, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy(C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkylthio, monofluoromethyl, difluoromethyl, trifluoromethyl and (C3-C6) cycloalkyl groups,
with a group xe2x95x90CYZ [Y and Z being chosen, independently of each other, from hydrogen atoms, halogen atoms and (C1-C4)alkyl groups (optionally substituted with 1 to 3 halogen atoms)],
or a 1,2,3,6-tetrahydropyridyl group optionally substituted with a (C1-C4)alkyl group (this (C1-C4)alkyl group being optionally substituted with 1 to 3 halogen atoms) or a (C3-C6)cycloalkyl group,
or a hexahydro-1H-azepinyl group optionally substituted in position 4 with a trifluoromethyl or difluoromethylene group,
or a group 
xe2x80x83in which
R12 is a (C1-C4)alkyl group, a carboxy(C1-C4)alkyl group or a (C1-C4)alkoxycarbonyl (C1-C4)alkyl group and R13 is a (C1-C4)alkoxy or (C1-C4)alkyl group,
or a piperazinyl group optionally substituted with a (C1-C4)alkyl group or a (C1-C4)alkylsulphonyl group,
or a morpholinyl group,
R3 represents
either a (C1-C5)alkyl group,
or a group xe2x80x94COR1, in which R1 is either a hydrogen atom or a group (C1-C4)alkyl, xe2x80x94(CH2)nOCH3, xe2x80x94CH2O(C2H4O)nCH3, xe2x80x94(CH2)nCF3 or xe2x80x94(CH2)nOH (n=1 to 4).
Among the preferred compounds defined above, the ones that are particularly preferred are the compounds of formula [I] in which:
X, R4 and B are as defined above,
W represents a xe2x80x94(CH2)3xe2x80x94 or xe2x80x94CH2xe2x80x94CHxe2x95x90CHxe2x80x94 (double bond in cis or trans configuration) group,
R2 represents
either a piperidyl group which is optionally substituted:
with one or two groups chosen from hydroxyl, (C1-C4)alkyl, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy(C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkylthio, monofluoromethyl, difluoromethyl and trifluoromethyl groups,
with a group xe2x95x90CYZ [Y and Z being chosen, independently of each other, from hydrogen atoms, halogen atoms and (C1-C4)alkyl groups (optionally substituted with 1 to 3 halogen atoms)],
or a 1,2,3,6-tetrahydropyridyl group optionally substituted with a (C1-C4)alkyl group (this (C1-C4)alkyl group being optionally substituted with 1 to 3 halogen atoms),
or a hexahydro-1H-azepinyl group,
or a piperazinyl group optionally substituted with a (C1-C4)alkylsulphonyl group,
or a morpholinyl group,
R3 represents a group xe2x80x94COR1, in which R1 is a group (C1-C4)alkyl, xe2x80x94(CH2)nOCH3 or xe2x80x94(CH2)nCF3 (n=1 to 4),
A represents
either a phenyl group optionally substituted with 1 to 3 substituents chosen from
a halogen atom and
(C1-C4)alkyl and (C1-C4)alkoxy groups,
or a heterocycle chosen from pyridyl and thienyl groups,
or a (C5-C8)cycloalkyl group.
The preferred configuration of the central amino acid portion of the compounds in accordance with the present invention: 
is [S]
The compounds of formula [I] in accordance with the invention may exist in the form of racemates or pure enantiomers or mixtures of enantiomers. They may also exist in the form of acids or free bases or addition salts with pharmaceutically acceptable acids, for example in the form of hydrochloride or methanesulphonate.
Mention may be made in particular of the following compounds, in the form of racemates or pure enantiomers or mixtures of enantiomers, or alternatively in the form of acids or free bases, of hydrochloride or of any other pharmaceutically acceptable salt, which form a part of the invention:
N-[2-[[[(1S)-4-(5-amino-3-methylpyrid-2-yl)-1-[[4-(difluoromethylene)piperid-1-yl]carbonyl]butyl]amino]sulphonyl]-6-thien-2-ylphenyl]propanamide,
N-[2-[[[(1S)-4-(6-amino-4-ethylpyrid-3-yl)-1-[[4-(difluoromethylene)piperid-1-yl]carbonyl]butyl]amino]sulphonyl]-6-cyclopentylphenyl]acetamide,
N-[3-[[[(1S)-4-(5-aminopyrid-2-yl)-1-[[4-(difluoromethylene)piperid-1-yl]carbonyl]butyl]amino]sulphonyl]-3xe2x80x2-fluoro[1,1xe2x80x2-diphenyl]-2-yl]propanamide,
N-[3-[[[(1S)-4-(5-aminopyrid-2-yl)-1-[[4-(difluoromethylene)piperid-1-yl]carbonyl]butyl]amino]sulphonyl]-3xe2x80x2-fluoro[1,1xe2x80x2-diphenyl]-2-yl]acetamide,
N-[2-[[[(1S)-4-(5-aminopyrid-2-yl)-1-[(4-ethylpiperid-1-yl)carbonyl]butyl]amino]sulphonyl]-6-thien-2-ylphenyl]propanamide,
N-[2-[[[(1S)-4-(6-aminopyrid-3-yl)-1-piperid-1-yl-carbonyl)butyl]amino]sulphonyl]-6-cyclopentylphenyl]propanamide,
N-[2-[[[(1S)-4-(5-aminopyrid-2-yl)-1-[[4-(difluoromethylene)piperid-1-yl]carbonyl]butyl]amino]sulphonyl]-6-cyclopentylphenyl]propanamide,
N-[3-[[[(1S)-4-(5-aminopyrid-2-yl)-1-[[4-(difluoromethylene)piperid-1-yl]carbonyl]butyl]amino]sulphonyl][1,1xe2x80x2-diphenyl]-2-yl]acetamide,
N-[2-[[[(1S)-4-(6-aminopyrid-3-yl)-1-[[4-(difluoromethylene)piperid-1-yl]carbonyl]butyl]amino]sulphonyl]-6-thien-2-yl-phenyl]acetamide,
N-[2-[[[(1S)-4-(6-amino-4-methylpyrid-3-yl)-1-[[4-(difluoromethylene)piperid-1-yl]carbonyl]butyl]amino]sulphonyl]-6-thien-2-ylphenyl]propanamide,
N-[2-[[[(1S)-4-(6-aminopyrid-3-yl)-1-[[4-(difluoromethylene)piperid-1-yl]carbonyl]butyl]amino]sulphonyl]-6-cyclopentylphenyl]acetamide,
N-[2-[[[(1S)-4-(aminopyrid-3-yl)-1-[[4-(trifluoromethyl)-1,2,3,6-tetrahydropyrid-1-yl]carbonyl]butyl]amino]sulphonyl]-6-thien-2-yl-phenyl]propanamide,
N-[2-[[[(1S)-4-(6-aminopyrid-3-yl)-1-[[4-(difluoromethylene)piperid-1-yl]carbonyl]butyl]amino]sulphonyl]-6-cyclopentylphenyl]propanamide,
N-[3-[[[(1S)-4-(5-aminopyrid-2-yl)-1-[[4-(difluoromethylene)piperid-1-yl]carbonyl]butyl]amino]sulphonyl][1,1xe2x80x2-diphenyl]-2-yl]propanamide,
N-[2-[[[(1S)-4-(6-amino-4-methylpyrid-3-yl)-1-[[4-difluoromethylene)piperid-1-yl]carbonyl]butyl]amino]sulphonyl]-6-cyclopentylphenyl]propanamide,
N-[3-[[[(1S)-4-(6-aminopyrid-3-yl)-1-[[4-(difluoromethylene)piperid-1-yl]carbonyl]butyl]amino]sulphonyl]-3xe2x80x2-fluoro[1,1xe2x80x2-diphenyl]-2-yl]propanamide,
N-[2-[[[(1S)-4-(5-aminopyrid-2-yl)-1-[(4-methylpiperid-1-yl)carbonyl]butyl]amino]sulphonyl]-6-thien-2-ylphenyl]acetamide,
N-[2-[[[(1S)-4-(6-aminopyrid-3-yl)-1-[(4-ethylpiperid-1-yl)carbonyl]butyl]amino]sulphonyl]-6-thien-2-ylphenyl]propanamide,
N-[2-[[[(1S)-4-(6-aminopyrid-3-yl)-1-[(4-methylpiperid-1-yl)carbonyl]butyl]amino]sulphonyl]-6-cyclopentylphenyl]acetamide,
N-[3-[[[(1S)-4-(5-aminopyrid-2-yl)-1-[(4-methylpiperid-1-yl)carbonyl]butyl]amino]sulphonyl]-3xe2x80x2-methyl[1,1xe2x80x2-diphenyl]-2-yl]acetamide,
N-[3-[[[(1S)-4-(6-amino-4-methoxypyrid-3-yl-1-[[4-(difluoromethylene)piperid-1-yl]carbonyl]butyl]amino]sulphonyl][1,1xe2x80x2-diphenyl]-2-yl]propanamide,
N-[3-[[[(1S)-4-(5-aminopyrid-2-yl)-1-[(4-methylpiperid-1-yl)carbonyl]butyl]amino]sulphonyl]-3xe2x80x2-methyl[1,1xe2x80x2-diphenyl]-2-yl]propanamide,
N-[3-[[[(1S)-4-(5-aminopyrid-2-yl)-1-[(4-methylpiperid-1-yl)carbonyl]butyl]amino]sulphonyl]-3xe2x80x2-fluoro[1,1xe2x80x2-diphenyl]-2-yl]acetamide,
N-[3-[[[(1S)-4-(5-aminopyrid-2-yl)-1-[(4-methylpiperid-1-yl)carbonyl]butyl]amino]sulphonyl]-3xe2x80x2-methoxy[1,1xe2x80x2-diphenyl]-2-yl]propanamide,
N-[(1S)-4-(5-amino-2-pyridyl)-1-[[4-(difluoromethylene)-1-piperidyl]carbonyl]butyl]-2-(formylamino)-3xe2x80x2-methyl[1,1xe2x80x2-diphenyl]-3-sulphonamide,
N-[3-[[[(1S,3Z)-4-(5-amino-2-pyridyl)-1-[[4-(difluoromethylene)-1-piperidyl]carbonyl]-3-butenyl]amino]sulphonyl][1,1xe2x80x2-diphenyl]-2-yl]acetamide,
N-[3-[[[(1S,3Z)-4-(5-amino-2-pyridyl)-1-[(4-methyl-1-piperidyl)carbonyl]-3-butenyl]amino]sulphonyl][1,1xe2x80x2-diphenyl]-2-yl]acetamide.
A subject of the invention is also a medicinal product, characterized in that it contains at least one compound of formula (I) as defined above.
A subject of the invention is also a pharmaceutical composition, characterized in that it contains at least one compound of formula (I) as defined above, as well as at least one pharmaceutically acceptable excipient.
With reference to Scheme 1, in order to obtain the compounds of formula [I] in accordance with the present invention in which X represents a group xe2x95x90CR4xe2x80x94, a compound of formula [V] in which P1 is a protecting group for an amine function, in particular a tert-butoxycarbonyl (Boc) group, B and W are as defined above and P is either a protecting group such as phenylmethoxycarbonyl or a hydrogen atom, is reacted, in a step (i), with a compound of formula [VI], in which R2 is as defined above. A compound of formula [IV] is thus obtained, which is treated with hydrogen chloride in a step (ii) to give a compound of formula [III]. 
In a step (iii), the compound of formula [III] is coupled, in the presence of triethylamine, with a compound of formula [II] in which R1, R4 and A are as defined above, to give, after treatment with ammonia, a compound of formula [I]. The modification of the group xe2x80x94NHCOR1 into a group xe2x80x94NHR3 as defined above in relation to formula [I] is carried out according to the techniques of organic chemistry that are known to those skilled in the art.
When it is desired to obtain a compound of formula [I] in which R4 is a hydrogen atom, a hydrogenolysis of compound [I] is then carried out in a step (iv) to give a compound of formula [Ib].
According to one preferred embodiment of the process for preparing the compounds of formula (I) of the present invention,
the step (i) mentioned above may be carried out in the presence of N,N-diisopropylethylamine (DIEA) in dichloromethane or in dimethylformamide by adding, under nitrogen, O-(1-benzotriazolyl)-N,N,Nxe2x80x2,Nxe2x80x2-tetramethyluronium hexafluorophosphate (HBTU),
step (ii) may be carried out in dichloromethane in the presence of hydrogen chloride gas,
step (iii) may be carried out first in dichloromethane and triethylamine (TEA) and then by taking up the product obtained in tetrahydrofuran (THF) and then passing a stream of ammonia through, followed by treatment with 0.1 N hydrogen chloride in isopropanol, or with hydrogen bromide in acetic acid,
step (iv) may be carried out by taking up the compound of formula [I] in a 0.1 N solution of hydrogen chloride and in isopropanol.
According to one variant of the process in accordance with the present invention, the compounds of formula [I], in which X represents a group xe2x95x90CR4xe2x80x94, are also prepared in accordance with Scheme 2. With reference to Scheme 2, these compounds may be prepared by reacting, in a step (i), the compound of formula [III] as obtained in step (ii) of the process of the invention described above (Scheme 1) [with P=a hydrogen atom] with a compound of formula [IIa], in which R4 is a halogen atom and R1 is as defined above. A compound of formula [Ia] is thus obtained, which is coupled with a compound of formula [VII] in which A is as defined above and R5 is a (C1-C4)alkyl group, to give a compound of formula [I]. When it is desired to obtain a compound of formula [I] in which R4 is a hydrogen atom, a hydrogenolysis of compound [I] is then carried out in a step (iii) to give a compound of formula [Ib].
According to one preferred embodiment of this variant of the process for preparing the compounds of formula [I] of the present invention, in which X represents a group xe2x95x90CR4xe2x80x94,
step (i) mentioned above may be carried out first in dichloromethane, in the presence of triethylamine, and then by next taking up the product obtained in a stream of ammonia, 
step (ii) may be carried out in a mixture of copper iodide and triphenylarsine (Ph3As) in anhydrous dimethylformamide (DMF) and by adding bisdibenzylideneacetonepalladium (0) [Pd(dba)2],
step (iii) may be carried out in the presence of active palladium-on-charcoal (Pd-c), and ammonium formate in methanol,
step (iv) may be carried out by taking up the compound of formula [I] in a 0.1 N solution of hydrogen chloride and in isopropanol.
The compounds of formula [V] of the present invention, as represented in Scheme 1, are prepared according to Schemes 3 and 4.
Schemes 3 and 4 illustrate the preparation of various types of compounds of formula [V], namely:
the compound of formula [Ve], which is useful as an intermediate in the preparation of compounds of formula (I) in which W=CH2xe2x80x94CHxe2x95x90CHxe2x80x94 (the double bond being in cis configuration),
the compound of formula [Vg], which is useful as an intermediate in the preparation of compounds of formula (I) in which W=xe2x80x94CH2xe2x80x94CHxe2x95x90CHxe2x80x94 (the double bond being in trans configuration),
the compound of formula [Vh], which is useful as an intermediate in the preparation of compounds of formula (I) in which W=xe2x80x94(CH2)3xe2x80x94,
the compound of formula [Vc], which is useful as an intermediate in the preparation of compounds of formula (I) in which W=CH2xe2x80x94Cxe2x89xa1Cxe2x80x94,
the compound of formula [Vi], which is useful as an intermediate in the preparation of compounds of formula (I) in which W=xe2x80x94(CH2)2xe2x80x94. 
To prepare the compound of formula [Vc], the following steps are carried out, for example (Scheme 3):
in a step (i), and by analogy with the synthesis disclosed in patent application WO 97/40052, a compound of formula [Va] in which P1 is as defined above, is reacted with a compound of formula [Vb] in which B1 is an aromatic base bearing either a protected or unprotected primary or secondary amine function, or a precursor of an amine function such as a nitro group, and X represents a halogen atom, to give a compound of formula [Vc].
To convert the compound of formula [Vc] into a compound of formula [V] which may be used directly in the process represented in Scheme 1, a saponification of the ester group is carried out, and, when B1 bears a precursor of an amine function, this precursor is converted into an amine group optionally protected with a group P, by means of the techniques of organic chemistry that are known to those skilled in the art.
To prepare the compound of formula [Vh], the following steps are carried out, for example (Scheme 3):
in step (ii), the compound of formula [Vc] is subjected either to a total hydrogenation, both of the triple bond and of the nitrogen heterocycle, optionally followed by a conventional orthogonal protection of the non-aromatic secondary amine which may be generated, with a group P such as phenylmethoxycarbonyl, or to a selective hydrogenation of the triple bond, followed by a saponification, to give the compound of formula [Vh].
To prepare the compound of formula [Ve], the following steps are carried out, for example (Scheme 3):
in a step (iii), compound [Vc] is subjected to a controlled hydrogenation of the triple bond, optionally followed by a conventional orthogonal protection of the secondary amine of the amine borne by the group B, with a group P such as tert-butoxycarbonyl (Boc). In a step (iv), a saponification of the ester group of compound [Vd] is carried out to give compound [Ve].
To prepare the compound of formula [Vg], the following steps are carried out, for example (Scheme 3):
in a step (v), compound [Va] is subjected first to a hydrostannylation of the triple bond, followed by a catalysed coupling via a palladium complex with a compound [Vb] in which B1 is an aromatic base bearing either a protected or unprotected primary or secondary amine function, or a precursor of an amine function such as a nitro group, and X represents a halogen atom, to give the compounds of formula [Vf],
in a step (vi), the ester group of the compound [Vf] is hydrolysed to give the compound of formula [Vg].
According to one preferred embodiment of the process for preparing the compounds of formula [V] of the present invention, as illustrated in Scheme 3:
step (i) mentioned above may be carried out in dimethylformamide, in the presence of a palladium-based catalyst such as the dichlorobis(triphenylphosphine)palladium/cuprous iodide complex, in basic medium, for example with potassium bicarbonate and in anhydrous dimethylformamide,
step (ii) mentioned above may be carried out with molecular hydrogen or ammonium formate, in methanol, in the presence of a palladium-based catalyst such as active palladium-on-charcoal, and by carrying out the saponification with lithium hydroxide in a methanol/water mixture,
step (iii) mentioned above may be carried out in the presence of palladium on barium sulphate in ethyl acetate. When B1 bears a nitro function, it is desirable to reduce it beforehand, preferably with iron in an ethanol/acetic acid mixture,
step (iv) leading to the compounds [Ve] may be carried out with lithium hydroxide in a methanol/water mixture,
step (v) may be carried out with a compound [Va] bearing a protecting group P1 such as trityl in order to improve the regioselectivity of the hydrostannylation reaction. This is carried out with tributyltin hydride in tetrahydrofuran in the presence of tetrakis(triphenylphosphine)palladium (0). The coupling with the electrophilic reagent [Vb] is carried out in anhydrous dioxane in the presence of tetrakis(triphenylphosphine)palladium (0),
when the group P1 of the compound of formula [Vf] is a trityl, step (vi) consists in converting the group P1 of trityl type into a tert-butyloxycarbonyl group in the presence of aqueous sodium hydroxide using bis(di-tert-butyl) carbonate. In this operation, the methyl ester is hydrolysed to carboxylic acid, thus giving the compound of formula [Vg].
With reference to Scheme 4, the intermediate compounds of formula [Vi] may be prepared, thus making it possible to prepare the compounds of formula [I] in which W is a xe2x80x94(CH2)2xe2x80x94 group, in the following way:
in a step (i), a compound of formula [VII] derived from glutamic acid, in which P1 is as defined above and Ph represents a phenyl group, is subjected to a Hunsdiecker reaction to give the compound of formula [VIII],
in a step (ii), the compound of formula [VIII] is converted into the corresponding organozinc derivative, which is coupled in situ, via catalysis with palladium, to a compound of formula [Vb] in which B1 is as defined above and X represents a halogen atom, to give the compounds of formula [IX],
in a step (iii), the compound of formula [IX] is hydrogenated on a palladium catalyst to give the compound of formula [Vi] bearing a free carboxylic acid function.
According to one preferred embodiment of this process for preparing the compounds of formula [Vi] of the present invention,
step (i) mentioned above may be carried out in carbon tetrachloride under argon, in the presence of di(acetyloxy)iodobenzene and molecular iodine. This step is thus carried out under UV irradiation,
step (ii) mentioned above may be carried out in dimethylformamide under argon in the presence of zinc powder activated by adding trimethylsilyl chloride and 1,2-dibromoethane. The organozinc derivative thus prepared is then treated with the electrophile B1X, for example in the presence of tris(dibenzylideneacetone)dipalladium and tri-ortho-tolylphosphine at room temperature,
step (iii) mentioned above may be carried out in a methanol/water mixture in the presence of active 10% palladium-on-charcoal catalyst and at 50 psi of hydrogen.
With reference to Scheme 5, in order to obtain the compounds of formula [XV], which are useful as intermediates for preparing the compounds of formula [I] in accordance with the invention in which X=N, the following steps are carried out:
in a step (i), a 4-aminopyridine compound of formula [X] in which the amine function is protected with a protecting group P1 as defined above, is converted into a derivative of formula [XI] bearing two bromine atoms positioned beforehand to introduce the desired groups,
in a step (ii), the compound of formula [XI] is coupled with a boronic acid derivative of formula AB(OH)2 in which A is a phenyl nucleus or a heterocycle which is optionally substituted, in the presence of a palladium catalyst, to give a compound of formula [XII], 
in a step (iii), the sulphur atom which is the precursor of the sulphonyl chloride group is introduced via a palladium-catalysed coupling reaction between the compound of formula [XII] and an organotin derivative prepared beforehand from benzenemethanethiol,
in a step (iv), the protecting group P1 is removed by acidic treatment under conventional conditions to give the compound of formula [XIV],
in a step (v), the compound of formula [XIV] is converted into a mixed imide by treatment with an anhydride, and the benzylthiol group is then directly oxidized to the chlorosulphonyl derivative of formula [XV] with sulphuryl chloride in the presence of acetic acid and water.
According to one preferred embodiment of this process for preparing the compounds of formula [XV]:
step (i) mentioned above may be carried out in acetonitrile with N-bromosuccinimide,
step (ii) mentioned above may be carried out in a dioxane/water mixture in the presence of sodium carbonate and tetrakis(triphenylphosphine)palladium (0),
step (iii) mentioned above may be carried out in anhydrous dioxane in the presence of tetrakis(triphenylphosphine)palladium (0) with tributyl[(phenylmethyl)thio]stannane prepared beforehand,
step (iv) mentioned above may be carried out conventionally in methanol in the presence of a stream of hydrogen chloride,
step (v) mentioned above may be carried out by heating in a pure anhydride such as propionic anhydride. After evaporating off the excess reagent, a treatment in a mixture of acetic acid and water with sulphuryl chloride gives the expected chlorosulphonyl compound of formula [XV] directly.
The compound of formula [XV] thus obtained may then be used to prepare the compounds of formula [I] in accordance with the invention in which X=N, by following the protocol described in step (iii) of Scheme 1, i.e. by coupling the compound of formula [XV] with a compound of formula [III] as defined above.
The starting compounds, such as the compound of formula [Vb] are commercially available or are described in the literature, or alternatively may be prepared according to methods which are described therein or which are known to those skilled in the art.